Information Resources for
Clinical Research
Josh Duberman, MLIS
Informationist / Research Librarian, NIH Library,
Introduction to the Principles & Practices of Clinical
Research (IPPCR), National Institutes of Health
(NIH), 2/14/11
Johns Hopkins University (JHU) 2001 Asthma Study
Healthy volunteer died after being administered hexamethonium by inhalation
PI didn’t find potential toxicity despite
“standard PubMed search” &
consulting “standard current editions of textbooks
of pharmacology & pulmonary medicine”
JHU Report, 7/01: Report of Internal Investigation into the Death of a Volunteer Research Subject, Johns Hopkins University, 7/01, http://www.hopkinsmedicine.org/press/2001/JULY/report_of_internal_investigation.htm
also see: J Savulescu and M Spriggs, The Hexamethonium Asthma Study and the Death of a Normal Volunteer in Research, J. Med. Ethics, 2002; 28;3-4 , http://jme.bmj.com/cgi/content/full/28/1/3
JHU 2001 Asthma Study – results
JHU research oversight improved
“requiring investigators to collaborate with a librarian and a pharmacist to strengthen literature searches… to help search appropriate databases for potential side effects.”
Hopkins Response to FDA Observations, JHMI Office of
Communications and Public Affairs, 9/7/01, http://www.hopkinsmedicine.org/press/2001/SEPTEMBER/010907A.htm
Guidelines established at JHU & elsewhere
Guidelines for Determining an Adequate and Comprehensive Literature Search of Drug and Device Safety for Use by Investigator and Institutional Review Boards, Institutional Review Board, Mount Sinai School of Medicine, 1/03,
http://www.mssm.edu/static_files/Old%20Sites/www.mssm.edu/cmca/pdf/SearchGuidelines.pdf (class handout)
Intro to Information Sources
Health Care Specialists’ Use of Online Info Resources
Literature Databases 90%
Online Journals 83%
Physician Portals 73%
Government Web Sites 61%
Manufacturers’ Web Sites 41%
Medical/professional Blogs 37%
Sept 2008 Survey of 255 medical specialists by Jupiter Research, "U.S. Online Specialists Executive Survey, 2008", as quoted in “Which Online Resources Do Online Health Care Specialists Use?”, iHealthBeat, 1/7/09; http://www.ihealthbeat.org/Data-Points/2009/Which-Online-Resources-Do-Online-Health-Care-Specialists-Use.aspx , accessed 2/15/09
Classifying Information Sources
Classic - Proximity to Source Material
original publications & data
bibliographic databases & indexing/abstracting services
reviews & reference works, textbooks
Practical - Content & Search Capabilities
subjects covered, in what degree of comprehensiveness
full text of articles vs. titles / keywords / abstracts
search technology & interface: structured indexing terms, thesaurus, wildcards, Boolean logic
update frequency, reliability, reproducibility
Format & Access - sources readily available to you or to patients
online vs. paper formats (or the heritage of printed formats)
items in your collection vs. items to be ordered
“free” vs. fee - Patients more likely to get info from free sources
Business Model – Who Pays? Affiliations/Sponsorship/Bias?
Familiarity
Sources you know about, & know how to search
Sources you’ve heard about
Keeping up with changing info landscape
Focus - searching for adverse effects & protocol development
Relevant to textbook chapters:
3 - Researching a Bioethical Question
8 - Unanticipated Risk in Clinical Research
16 - Design & Conduct of Observational
Studies & Clinical Trials
24 - Writing a Protocol
Principles and Practice of Clinical Research,
JI Gallin & FP Ognibene, eds., 2nd ed., Elsevier, 2007
PubMed
US National Library of Medicine (NLM) database – refers to >20 M articles from 5,400 biomedical journals in 39 languages
medicine, nursing, dentistry, veterinary medicine, allied health & pre-clinical sciences
currently includes references from 1948 - present, with some older items
free online – www.pubmed.gov ; NIH staff should click
“PubMed@NIH” at the NIH Library web site http://nihlibrary.nih.gov
to enable full text access to subscribed journals
bibliographic database with author-provided abstracts
added indexing terms - MeSH (Medical Subject Headings) thesaurus
links to other resources
• PubMed – cont’d
JHU internal investigation found different PubMed results depending on the terms searched
• possibly due in part to limited coverage of older material & classification changes over time
Terms searched # Results # Useful
hexamethonium inhalation lung injury => 0 hits
hexamethonium inhalation => 42 hits 0
hexamethonium lung => not reported 3
hexamethonium lung toxicity => 4 hits 0
hexamethonium lung hypersensitivity => 16 hits 3
hexamethonium lung fibrosis => 3 hits 2
JHU Report, 7/01
Basic Searching Tips
How Search Works – typically every word in record is indexed & the index is searched; success depends on:
File content or scope
Individual record content (bibliographic info, abstract if avail.,indexing/keywords)
Problem of categories & group names - thesauri, classification schemes
Transparency/reproducibility of search algorithms & processes
Additional search terms automatically added – plurals, synonyms, etc.
Build concept-based searches - first broaden, then narrow
use synonyms & group similar concepts together: (A or B) and C
(ganglionic blockers OR hexamethonium) AND lung
PubMed - Older Information
PubMed now covers back to 1948 with some earlier coverage; older information is available in print sources – 3 relevant examples:
“Lung Changes During Hexamethonium Therapy for Hypertension”, British Heart J., 1954 – key article but
‘toxicity’ or ‘adverse effects’ not in PubMed record
phrase “hexamethonium lung” in titles of 2 articles from 1956 & 1962 - indexing included ‘toxicity’ or ‘adverse effects’
Cited reference searching could provide additional access - more recent articles refer to older articles
1966 and all that--when is a literature search done?, F McLellan, The Lancet, August 25, 2001, v358 i9282 p646
PubMed - Searching
Understand PubMed to get comprehensive results
Search Aids available by clicking “Help” - online book
includes Quick Start & FAQs at lower left
“PubMed Tutorials” - web-based & interactive
Distance Education Program Resources –online training, webcasts,
tutorials & handouts - http://www.nlm.nih.gov/bsd/dist_edu.html
NLM Training Manuals http://www.nlm.nih.gov/pubs/web_based.html
MeSH - added subject headings - often change over time
My NCBI – save searches, get updates while trial is in progress
Limits - not always obvious; “clinical trial” limits don’t include all observational studies
Advanced Search: Search Builder – combine search results;
Details - shows what was searched;
Use “ ” to ensure phrase (string) searching
Screenshot: http://nihlibrary.nih.gov
Screenshot:
Public access at www.pubmed.gov
Screen shot: PubMed search
Screen shot: PubMed search
Screenshot: PubMed search results
Screenshot: PubMed search results
Screenshot: PubMed advanced search details
Screenshot: PubMed Advanced Search
Screenshot: PubMed search
Screenshot: PubMed search results
Screen shot: PubMed search results
Screenshot: PubMed search results
Screenshot: Pubmed search result
More Information Sources
Comprehensive searches usually require multiple information sources
Different sources have areas of specialization but may overlap
Many sources are fee-based, & only available by subscription
check your library/organization for institutional subscriptions
Examples of some information sources follow; see websites for tutorials & more information
different versions of these sources may be available with varying coverage and capabilities
many other sources may also be important for a given search
Embase™
Covers pharmacological & biomedical literature, with >24M records > 7,500 journals, 34 languages
key clinical medicine database, European based
NIH-accessible file www.embase.com covers 1947 – present
User guides http://info.embase.com/user_support/learning_tools.shtml
Includes all of PubMed, as well as additional material, but with different indexing & twice as many thesaurus terms (EMTREE)
Especially useful for drug side effects/interactions, toxicology, biotechnology, medical devices, health policy/management, public/occupational/environmental health, conferences, & alternative/complementary medicine
Embase™ vs PubMed
“Lung Changes During Hexamethonium Therapy for Hypertension”, British Heart J, 1954 PubMed – doesn’t include abstract, ‘toxicity’ or ‘adverse effects’ Embase – includes abstract, ‘dyspnea’ & ‘edema’ (& British spellings)
“Hexamethonium lung; report of a case associated with pregnancy”, J Obstet Gynaecol Br Emp, 1956 PubMed – no abstract, but good MeSH indexing terms – Hexamethonium Compounds/*adverse effects
Embase – includes ‘edema’ & abstract: “…a woman of 37, treated with hexamethonium compounds for severe hypertension during ... pregnancy. She died after the birth of a live infant…Treatment with hexamethonium drugs… from the 17th week. Severe, ultimately fatal, respiratory disease developed during the 35th week…”
Screenshot: Emabse search results
Screenshot: Emabase search results
Micromedex(R)
summaries & detailed monographs for drugs, diseases, alternative medicine, toxicological managements, emergency care & reproductive risks – see http://www.micromedex.com/products/hcs/ &
http://www.micromedex.com/support/training/HCSkit/
“had lung toxicity as the first side effect of hexamethonium” (JHU Report, 7/01)
BIOSIS Previews (R)
biological, biomedical & life science research - traditional, experimental & interdisciplinary subjects & technical notes/letters - includes NIH-accessible file Biological Abstracts® - see http://www.thomsonreuters.com/products_services/scientific/BIOSIS_Previews
• Cited Reference Searching
Web of Science (R) – includes multidisciplinary indexes;
Science Citation Index Expanded®, > 7,100 journals, 1900 - present
Social Sciences Citation Index®, >2,100 journals, 1956 – present
complete citation counts for all records; many lack abstracts/indexing
http://thomsonreuters.com/products_services/science/science_products/a-z/web_of_science/
Scopus (R) – scientific, technical, medical, & social science literature; includes patents & Scirus websearch engine, see http://www.scopus.com
>16,000 journals from 1823 – present; many records include abstracts
complete citation counts from 1996 – present
Both are also useful for conference coverage &
citation counts/ranking
Evidence-Based Information
Cochrane Library – http://www.cochrane.org/ - Regularly updated collection for practitioners & policy makers, includes:
evidence-based medicine reviews (systematic reviews)
effectiveness of health care interventions &
clinical trial registry (published/unpublished)
Guidelines.gov - evidence-based guideline clearinghouse
from the Agency for Healthcare Research & Quality (AHRQ),
US Dept of Health & Human Services, www.guidelines.gov
Screenshot: Cochrane Library search results
Screenshot: Agency for Healthcare Research and Quality National Guideline for Clearinghouse
Clinical Trial Information
ClinicalTrials.gov - NIH clinical trials list www.clinicaltrials.gov
CenterWatch - commercial Clinical Trials Listing Service™ http://www.centerwatch.com/
International Clinical Trials Registry Platform (ICTRP) – World Health Organization http://www.who.int/ictrp/en/
Note: Many trials are not properly registered - S. Mathieu et al., Comparison of registered and published primary outcomes in randomized controlled trials, JAMA 2009:302(9):977-984, PMID 19724045, http://www.ncbi.nlm.nih.gov/pubmed?term=19724045
TOXNET - http://toxnet.nlm.nih.gov cluster of databases covering toxicology, hazardous chemicals, environmental health & related areas from NLM - see http://www.nlm.nih.gov/pubs/factsheets/toxnetfs.html ToxSeek http://toxseek.nlm.nih.gov - meta-search engine, includes TOXNET, PubMed, PMC, Bookshelf, ClinicalTrials & others
Texts & References – either in print or online:
NCBI Bookshelf – free online books, available by clicking the arrow above the PubMed search window to search ‘Books’-
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books
Hexamethonium toxicity wasn’t mentioned in the last 4
editions of Goodman & Gillman, or in the current edition of Fishman’s Pulmonary Medicine – but was included in a previous edition of Fishman’s text (JHU Report, 7/01)
Screenshot: TOXNET Toxicology Data Network
Screenshot: ToxSeek search results
Screenshot: ToxSeek search results
Specialized sources
Regulatory information – MedWatch - post-marketing surveillance from pharmaceutical companies, required by FDA http://www.fda.gov/medwatch/index.html (textbook pp.397-399)
Engineering databases - Compendex® & Inspec® information on medical devices
Others:
• patent literature
• drug pipeline (drugs in development) databases
• chemistry databases (Chemical Abstracts, etc.)
Screenshot: FDA
MedWatch: The FDA Safety Information and Adverse Event Reporting Program
Free full text on the internet
Increasing amount of readily available information
PubMed/MEDLINE – can limit to items with links to free full text
PubMed Central (PMC) – free digital biomedical/life sciences journal literature archive from NIH, >2M full text articles (>10% of PubMed) ; http://www.pubmedcentral.nih.gov/
Includes BioMed Central, http://www.biomedcentral.com/ , Public Library of Science, http://www.plos.org/ , & mandated public access to NIH-funded research
Directory of Open Access Journals – many are full text searchable - http://www.doaj.org/
MedlinePlus – consumer health information, NLM http://medlineplus.gov/
Internet Search Engines
Google, Google Scholar, Yahoo & others – access increasing amounts of information, some in full text
JHU PI found first evidence of hexamethonium pulmonary toxicity on the internet
Google and Yahoo found a hexamethonium toxicity site, but other search engines didn’t (JHU Report, 7/01)
Search most effectively with advanced search features
change preferences to see more, with less work
use different search engines for different scope/coverage, search
capabilities, & ranking algorithms
Google & Google Scholar
Google www.google.com; Advanced http://www.google.com/advanced_search?hl=en http://www.google.com/support/websearch/bin/answer.py?hl=en&answer=136861 ; Preferences www.google.com > Search settings > Number of Results > change ‘Display’ from 10 to 100 if “Do not use Google Instant” is clicked
Google Scholar http://scholar.google.com/ full text journal articles, books, patents, & dissertations ; Advanced http://scholar.google.com/advanced_scholar_search & http://scholar.google.com/intl/en/scholar/refinesearch.html ; Preferences http://scholar.google.com/scholar_preferences > Library Links> Search for “NIH” > check box “NIH Library - Full-Text Plus!” > save ; also search “worldcat”, check box “Open WorldCat – Library Search’, > change ‘Number of Results’ from 10 to 100; possibly also check “Show links to import citations into EndNote” ; > save
Advanced Search Operators: “Phrase Search” within double quotes; Must include/exclude +/- plus or minus sign immediately preceeding included or excluded word (no spaces) ; site: URL must include word immediately following colon; filetype:ppt or filetype:pdf
Yahoo, Bing, Exalead & Blekko
Yahoo www.yahoo.com ;Advanced search.yahoo.com/web/advanced?ei=UTF-8 > change ‘Number of Results’ from 10 to 100; Preferences search.yahoo.com/preferences
Bing www.bing.com ; > Preferences > ‘Results’ change from 10 to 50; more information http://www.bing.com/explore?q=&FORM=BXLH ; after searching click ‘Advanced’ above results; or see http://bit.ly/BingAdvn
Exalead www.exalead.com/search -the only search engine which allows true proximity searching, truncation, & phonetic searching; Advanced > ‘advanced search’ >menu of options; Preferences www.exalead.com/account/preferences/ > change ‘Results per page’ from ‘10’ to ‘100’ > ‘Save my preferences’; Information > FAQ at bottom left
Blekko http://blekko.com/ - uses slashtags as additional descriptors; Information > ‘help’ at bottom – offers reliable date indexing
Google & other web resources
Why is the information provided?
What is the business model - who pays?
Incentives for accuracy and completeness?
Search Engine Optimization industry - examples discussed in
D. Segal, Search Optimization and Its Dirty Little
Secrets, NYT 2/12/11 http://nyti.ms/optimiz
Promising technology - increasingly powerful capabilities
Cautions include possible
inconsistent results,
lack of search documentation
lack of confidentiality
Bioinformatics Resources
NCBI resources - access by clicking arrow above PubMed search window http://www.ncbi.nlm.nih.gov/Sitemap/index.html – site map http://www.ncbi.nlm.nih.gov/Database/ - shows overview & linkage
“Human Genome Project and Clinical Research”, Dr Chris Austin, IPPCR lecture tomorrow 2/15/11
Bioinformatics Resources, Dr. Medha Bhagwat, IPPCR lecture 1/26/10 https://webmeeting.nih.gov/p19902251/ -(starts at 34 min); ppts at http://ippcr.nihtraining.com/lecture_detail.php?lecture_id=49&year=2009 – HUGE Navigator, OMIM & dbSNP – predict success of using buproprion to quit smoking
NIH Library http://nihlibrary.nih.gov/ResearchTools/Pages/Bioinformatics.aspx >Bioinformatics (quick link at left of home page) ; resources include http://nihlibrary.nih.gov/ResearchTools/Pages/biotutorials.aspx with links to free online tutorials from EBI, MIT & Harvard
Screenshot: NCBI Site Map
Screenshot: NCBI Site Map
Screenshot: Bioinformatics Research Tools
Screenshot: Bioinformatics Online Tutorials
Search Strategy & Updates
Ask the Right Questions – consider PICO outline & synonyms to help organize your thoughts, concepts & search terms: Patient/Population and/or Problem ; Intervention ; Comparison/Control ; Outcome or Effects - The Literature Searching Process Protocol for Researchers, Thames Valley Health Libraries Network, Mar. 2006, http://www.ieph.org/hase/Downloads/Lit_Search_Protocol_Researchers.pdf